Time-of-flight mass spectrometers are used as detectors for chromatographic separators, for example, in liquid chromatography (LC), gas chromatography (GC), and comprehensive two-dimensional chromatography (GC×GC). It is necessary to calibrate the mass scale or mass-to-charge scale of high resolution time-of-flight mass spectrometers for the purpose of accurate measurement of mass-to-charge ratios of ions appearing in mass spectra.
Mass calibration in prior art GC-HRTOFMS typically involves the following steps:
introducing a calibrant material, such as perfluorokerosene (PFK) or perfluorotributylamine (PFTBA), to the ion source for a period of time;
recording mass spectra of the calibrant material;
determining an empirical relationship between the m/Q ratios of calibrant ions and their measured times of flight;
stopping the introduction of the calibrant into the ion source;
admitting a sample for GC-HRTOFMS analysis; and
compensating for temporal drift during the analysis by monitoring a so-called “lock mass” throughout the run.
In stopping the introduction of the calibrant into the ion source during the fourth step of the procedure, calibrant material is removed from the ion source prior to the introduction of the sample, and is not re-introduced to the ion source until the analysis of the sample is completed. It is known that, over the course of a typical GC analysis, thermal drift in the temperature of the HRTOFMS flight tube will cause changes in its length due to thermal expansion or contraction, thereby inducing drift in times-of-flight. To compensate for this effect, it is common to monitor the time-of-flight of a particular ion, that is, of a so-called “lock mass.” This permits one parameter in the mathematical relationship between time-of-flight and m/z ratio to be compensated for drift. This procedure is referred to herein as “single-parameter drift compensation.”
Temperature change is not the only source of drift in time-of-flight mass spectrometers. To compensate for additional sources of drift it is necessary to monitor more than one “lock mass.” Ideally, in fact, one would monitor all ions normally employed for mass calibration, throughout the analytical run. This would permit frequent updating of as many of the mass calibration parameters as there are ions in the calibrant mass spectrum. By repeating such a mass calibration frequently throughout the analytical run, it would be possible to compensate for many possible sources of drift in time-of-flight measurements. Such a procedure is referred to herein as “multi-parameter drift compensation.”
One way to achieve multi-parameter drift compensation is to introduce mass calibrant material to the ions source of the HRTOFMS continuously throughout the analytical run, and to perform a large number of mass calibrations during the run. This procedure, however, is disadvantageous for two reasons. First, calibrant ions frequently interfere with analyte ions. Second, calibrant material in the ion source competes for ionizing agents, for example, 70 eV electrons in the case of electron impact ionization, or quasi-molecular ions in the case of chemical ionization. This competition lowers sensitivity. For these reasons, multi-parameter drift compensation is not practical in most analytical systems, especially in GC-HRTOFMS and in GC×GC×HRTOFMS. It would be useful, therefore, to introduce calibrant material during an analytical run, but in a manner that avoids mass interference and sensitivity loss.